Download Xyrem®, sodium oxybate, dru093

Medication Policy Manual
Policy No: dru093
Topic: Xyrem®, sodium oxybate
Date of Origin: September 12, 2003
Committee Approval Date: September 9, 2016
Next Review Date: September 2017
Effective Date: October 1, 2016
IMPORTANT REMINDER
This Medication Policy has been developed through consideration of medical necessity,
generally accepted standards of medical practice, and review of medical literature and
government approval status.
Benefit determinations should be based in all cases on the applicable contract language. To the
extent there are any conflicts between these guidelines and the contract language, the contract
language will control.
The purpose of Medication Policy is to provide a guide to coverage. Medication Policy is not
intended to dictate to providers how to practice medicine. Providers are expected to exercise
their medical judgment in providing the most appropriate care.
Description
Sodium oxybate (Xyrem®) is a medication used to reduce the number of cataplexy (weak or
paralyzed muscles) attacks and to reduce excessive daytime sleepiness in patients with
narcolepsy. Sodium oxybate is a schedule III controlled substance.
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Policy/Criteria
I.
Most contracts require prior authorization approval of sodium oxybate prior to coverage.
Sodium oxybate may be considered medically necessary for members with the following
diagnoses when criterion A or B below is met.
A.
Cataplexy (a sudden loss in muscle tone and deep tendon reflexes) associated
with narcolepsy.
OR
B.
Excessive daytime sleepiness associated with narcolepsy when:
1.
Modafinil in doses up to 400 mg daily, or armodafinil in doses up to 250
mg daily, has been ineffective, not tolerated, or contraindicated.
AND
2.
II.
III
Administration, Quantity Limitations, and Authorization Period
A.
OmedaRx considers sodium oxybate to be a self-administered medication.
B.
When prior authorization is approved, sodium oxybate may be covered in
quantities up to 9 grams per night.
C.
Authorization shall be reviewed at least annually to confirm that current medical
necessity criteria are met and that the medication is effective.
Sodium oxybate is considered not medically necessary for the following condition(s):
A.
IV.
At least one other formulary/preferred treatment, such as
methylphenidate or dextroamphetamine, has been ineffective, not
tolerated, or contraindicated.
Fibromyalgia.
Sodium oxybate is considered investigational for other conditions or applications,
including, but not limited to, the treatment of:
A.
B.
C.
D.
E.
F.
Alcohol dependence and withdrawal.
Myoclonus and essential tremor
Night eating syndrome.
Opioid dependence and withdrawal.
Parkinsonism.
Primary obstructive sleep apnea
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Position Statement
Clinical Efficacy
CATAPLEXY/ NARCOLEPSY
-
There is no useful evidence that sodium oxybate is more effective than oral stimulants,
such as methylphenidate, dexamphetamine, modafinil, or armodafinil, in relieving the
symptoms of cataplexy associated with narcolepsy or excessive daytime sleepiness
associated with narcolepsy.
*
In trials with uncertain usefulness, sodium oxybate showed statistically
significant reduction in the weekly cataplexy attacks compared to placebo after 4
weeks of treatment, by about 6 to 12 attacks per week, compared to patients
receiving placebo. Note that more than 80% of subjects were also taking
modafinil during the trial, making it impossible to separate the effect of each
medication. [1-5]
*
Patients with excessive daytime sleepiness randomized to sodium oxybate
showed a statistically significant, but modest improvement, in scores on rating
scales to assess sleepiness and maintenance of daytime wakefulness compared to
patients taking placebo after 8 weeks of treatment. Note that more than 75% of
subjects were also taking modafinil during the trial, making it impossible to
separate the effect of each medication. [1, 6, 7]
-
There is no useful evidence that combining sodium oxybate with modafinil substantially
reduces drowsiness over either agent alone. [1, 6]
-
There is no useful evidence to support use of sodium oxybate in the treatment of
conditions other than cataplexy in narcolepsy.
-
The safety and effectiveness of sodium oxybate doses > 9 grams per night have not been
established. [1]
FIBROMYALGIA
-
The most recent national fibromyalgia treatment guidelines from the American Pain
Society include the following recommendations: [8]
*
Non-drug therapies such as exercise and cognitive behavioral therapy are
recommended as a foundation of treatment.
*
Tricyclic antidepressants (TCAs) (e.g., amitriptyline, desipramine) or
cyclobenzaprine are considered first-line medication options, and provide the best
value for patients.
*
Serotonin reuptake inhibitors (e.g., fluoxetine) or tramadol (with or without
acetaminophen) may also be used with or without TCAs or cyclobenzaprine.
-
Sodium oxybate is not currently recognized as a treatment option for fibromyalgia in the
current national guidelines. [8]
-
Four published clinical trials have evaluated the efficacy of sodium oxybate in the
management of patients with fibromyalgia. [9-12] Although suggestive of efficacy, these
trials have significant flaws, including high rates of subject non-completion, which
makes the results of these trials uncertain.
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-
There is no evidence sodium oxybate is safer or more effective than standard treatments
for fibromyalgia.
Investigational Uses
ALCOHOL DEPENDENCE AND WITHDRAWAL
-
The evidence for the sodium oxybate in alcohol dependence and withdrawal is limited to
one small trial in outpatients, along with other very small trials generally administered
as part of an inpatient admission.
-
All four small randomized controlled trials have reported reduction of symptoms related
to alcohol withdrawal compared to placebo, clomethiazole, diazepam, or oxazepam. [13-15,
28]- These trials examined the use of sodium oxybate on alcohol craving, alcohol
consumption and/or abstinence. While suggestive of a useful effect, more studies are
needed to fully understand the role of sodium oxybate for the management of alcohol
abuse.
OBSTRUCTIVE SLEEP APNEA
-
Small, exploratory studies have been conducted to evaluate the safety of sodium oxybate
in patients with obstructive sleep apnea. [19]. Although suggestive, larger, better
designed randomized controlled trials are needed to evaluate whether the benefits of
sodium oxybate outweigh the risks in this patient population.
OTHER
-
Sodium oxybate has been studied in small, preliminary trials for possible efficacy in
opiate withdrawal syndrome, parkinsonism, essential tremor, and night-eating
syndrome. Further research is needed to establish the clinical safety and efficacy of
sodium oxybate for these indications. [20-25]
Safety
-
Contraindications to the use of sodium oxybate include: [1]
*
Concomitant treatment with sedative hypnotic agents.
Use in patients with succinic semialdehyde dehydrogenase deficiency. This rare
disorder is an inborn error of metabolism variably characterized by mental
retardation, hypotonia, and ataxia.
Boxed Warning [1]
*
-
*
Sodium oxybate should not be used with alcohol or other central nervous system
(CNS) depressants. It is the same chemical as gamma hydroxybutyrate (GHB), a
known drug of abuse. Abuse has been associated with some important CNS
adverse events (including death). Even at recommended doses, use has been
associated with confusion, depression and other neuropsychiatric events. Reports
of respiratory depression occurred in clinical trials. Almost all of the patients
who received sodium oxybate during clinical trials were receiving CNS
stimulants.
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-
*
Important CNS adverse events associated with abuse of GHB include seizure,
respiratory depression and profound decreases in level of consciousness, with
instances of coma and death. For events that occurred outside of clinical trials, in
people taking GHB for recreational purposes, the circumstances surrounding the
events are often unclear (e.g., dose of GHB taken, the nature and amount of
alcohol or any concomitant drugs).
*
Sodium oxybate is available through the Xyrem Success Program, using a
centralized pharmacy 1-866-XYREM88® (1-866-997-3688). The Success Program
provides educational materials to the prescriber and the patient explaining the
risks and proper use of sodium oxybate, and the required prescription form. Once
it is documented that the patient has read and/or understood the materials, the
drug will be shipped to the patient. The Xyrem Success Program also
recommends patient follow-up every 3 months. Physicians are expected to report
all serious adverse events to the manufacturer.
Deaths [26, 27]
Deaths have been reported in the literature associated with the therapeutic use of
sodium oxybate. These cases varied in diagnosis and individual circumstance, but
underscore the importance of using sodium oxybate only in clinical situations where
there is reliable clinical evidence that the benefit of treatment outweighs the risk.
Cross References
Nuvigil®, armodafinil, dru185
Provigil®, modafinil, dru058
Codes
Number
Description
N/A
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References
1. Xyrem® [package insert]. Palo Alto CA: Jazz Pharmaceuticals.; April 2015.
2. U.S. Xyrem Multicenter Study Group 1: Sodium oxybate demonstrates long-term efficacy for
the treatment of cataplexy in patients with narcolepsy. Sleep Med 2004;5:119-23.
3. Anonymous. A 12-month, open-label, multicenter extension trial of orally administered
sodium oxybate for the treatment of narcolepsy. Sleep 2003;26:31-5.
4. Anonymous. A randomized, double blind, placebo-controlled multicenter trial comparing the
effects of three doses of orally administered sodium oxybate with placebo for the treatment
of narcolepsy. Sleep 2002;25:42-9.
5. Xyrem International Study Group. Further evidence supporting the use of sodium oxybate
for the treatment of cataplexy: a double-blind, placebo-controlled study in 228 patients.
Sleep Med. 2005 Sep;6(5):415-21.
6. Black J, Houghton, WC. Sodium oxybate improves excessive daytime sleepiness in
Narcolepsy. Sleep. 2006 Jul 1;29(7):939-46.
7. Weaver TE, Cuellar N. A randomized trial evaluating the effectiveness of sodium oxybate
therapy on quality of life in narcolepsy. Sleep. 2006 Sep 1;29(9):1189-94.
8. Buckhardt CS, Goldenberg D, Crofford L, Gerwin R, Gowens S, et al. Guideline for the
management of fibromyalgia syndrome pain in adults and children: American Pain Society
(APS); 2005. 109 p. (Clinical practice guideline; no. 4).
9. Scharf MB, Baumann M, Berkowitz DV. The effects of sodium oxybate on clinical symptoms
and sleep patterns in patients with fibromyalgia. J Rheumatol 2003;30:1070-4.
10. Russell IJ, Perkins AT, Michalek JE; Oxybate SXB-26 Fibromyalgia Syndrome Study
Group. Sodium oxybate relieves pain and improves function in fibromyalgia syndrome: a
randomized, double-blind, placebo-controlled, multicenter clinical trial. Arthritis Rheum.
2009 Jan;60(1):299-309.
11. Spaeth M, Bennett RM, Benson BA, Wang YG, Lai C, Choy EH. Sodium oxybate therapy
provides multidimensional improvement in fibromyalgia: results of an international phase 3
trial. Ann Rheum Dis. 2012 June;71(6):935-42. PMID: 22294641
12. Russell IJ, Holman AJ, Swick TJ, Alvarez-Horine S, Wang YG, Guinta D; Sodium Oxybate
06-008 FM Study Group. Sodium oxybate reduces pain, fatigue, and sleep disturbance and
improves functionality in fibromyalgia: results from a 14-week, randomized, double-blind,
placebo-controlled study. Pain. 2011 May;152(5):1007-17. doi: 10.1016/j.pain.2010.12.022.
Epub 2011 Mar 11. PubMed PMID: 21397402.
13. Nimmerrichter AA, Walter H, Gutierrez-Lobos KE, Lesch OM. Double-blind controlled trial
of gamma-hydroxybutyrate and clomethiazole in the treatment of alcohol withdrawal.
Alcohol 2002;37:67-73.
14. Gallimberti L, Canton G, Gentile N, Ferri M, Cibin M, Ferrara SD, et al. Gammahydroxybutyric acid for treatment of alcohol withdrawal syndrome. Lancet
1989;2(8666):787-9.
15. Nava F, Premi S, Manzato E, Campagnola W, Lucchini A, Gessa GL. Gammahydroxybutyrate reduces both withdrawal syndrome and hypercortisolism in severe
abstinent alcoholics: an open study vs. diazepam. Am J Drug Alcohol Abuse. 2007;33(3):37992. PubMed PMID: 17613965.
16. Gallimberti L, Ferri M, Ferrara SD, Fadda F, Gessa GL. Gamma-Hydroxybutyric acid in the
treatment of alcohol dependence: a double-blind study. Alcohol Clin Exp Res 1992;16:673-6.
17. Nava F, Premi S, Manzato E, Lucchini A. Comparing treatments of alcoholism on craving
and biochemical measures of alcohol consumption. J Psychoactive Drugs. 2006
Sep;38(3):211-7.
18. Caputo F, Addolorato G, Stoppo M, et al., Alcohol Treatment Study Group. Comparing and
combining gamma-hydroxybutyric acid (GHB) and naltrexone in maintaining abstinence
from alcohol: an open randomised comparative study. Eur Neuropsychopharmacol. 2007
Dec;17(12):781-9.
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dru093.13
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19. George CF, Feldman N, Inhaber N, et al. A safety trial of sodium oxybate in patients with
obstructive sleep apnea: Acute effects on sleep-disordered breathing. Sleep Med. 2010
Jan;11(1):38-42. PubMed PMID: 19897413
20. Rosen MI, Pearsall HR, Woods SW, Kosten TR. Effects of gamma-hydroxybutyric acid
(GHB) in opioid-dependent patients. J Sub Abuse Treat 1997;14:149-54.
21. Gallimberti L, Cibin M, Pagnin P, Sabbion R, Pani PP, Pirastu R, et al. Gammahydroxybutyric acid for treatment of opiate withdrawal syndrome.
Neuropsychopharmacology 1993;9:77-81.
22. Volpi R, Chiodera P, Caffarra P, Scaglioni A, Malvezzi L, Saginario A, Coiro V. Muscarinic
cholinergic mediation of the GH response to gamma-hydroxybutyric acid: neuroendocrine
evidence in normal and parkinsonian subjects. Psychoneuroendocrinology 2000;25:179-85.
23. Mazzetti di Pietralata M, Florentino MT, Guidi M, Leonardi C. Night eating syndrome.
Preliminary results. Eat Weight Disorders 2000;5:92-101.
24. Frucht SJ, Houghton WC, Bordelon Y, Greene PE, Louis ED. A single-blind, open-label trial
of sodium oxybate for myoclonus and essential tremor. Neurology. 2005 Dec 27;65(12):19679.
25. Ondo WG, Perkins T, Swick T, et al. Sodium oxybate for excessive daytime sleepiness in
Parkinson disease: an open-label polysomnographic study. Arch Neurol. 2008
Oct;65(10):1337-40.
26. Zvosec DL, Smith SW, Hall BJ. Three deaths associated with use of Xyrem. Sleep Med. 2009
Apr;10(4):490-3. Epub 2009 Mar 9.
27. Akins BE, Miranda E, Lacy JM, Logan BK. A multi-drug intoxication fatality involving
Xyrem (GHB). J Forensic Sci. 2009 Mar;54(2):495-6.
28. Caputo F, Skala K, Mirijello A, Ferrulli A, Walter H, Lesch O, Addolorato G. Sodium
oxybate in the treatment of alcohol withdrawal syndrome: a randomized double-blind
comparative study versus oxazepam. The GATE 1 trial. CNS Drugs. 2014 Aug;28(8):743-52.
doi: 10.1007/s40263-014-0183-1. PubMed PMID: 24996524.
Revision History
Revision Date
Revision Summary
09/09/2016
No criteria changes with this annual update
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